Examining Host and Microbial Determinants of <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> Induced Delayed Wound Healing
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| Language: | English |
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The Ohio State University / OhioLINK
2017
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1483043104121139 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu1483043104121139 |
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English |
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Veterinary Services Microbiology Pseudomonas aeruginosa Staphylococcus aureus neutorphil chronic wound transposon sequencing porcine pig model cytokine histopathology burn wound |
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Veterinary Services Microbiology Pseudomonas aeruginosa Staphylococcus aureus neutorphil chronic wound transposon sequencing porcine pig model cytokine histopathology burn wound Chaney, Sarah B. Examining Host and Microbial Determinants of <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> Induced Delayed Wound Healing |
| author |
Chaney, Sarah B. |
| author_facet |
Chaney, Sarah B. |
| author_sort |
Chaney, Sarah B. |
| title |
Examining Host and Microbial Determinants of <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> Induced Delayed Wound Healing |
| title_short |
Examining Host and Microbial Determinants of <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> Induced Delayed Wound Healing |
| title_full |
Examining Host and Microbial Determinants of <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> Induced Delayed Wound Healing |
| title_fullStr |
Examining Host and Microbial Determinants of <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> Induced Delayed Wound Healing |
| title_full_unstemmed |
Examining Host and Microbial Determinants of <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> Induced Delayed Wound Healing |
| title_sort |
examining host and microbial determinants of <i>pseudomonas aeruginosa</i> and <i>staphylococcus aureus</i> induced delayed wound healing |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2017 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1483043104121139 |
| work_keys_str_mv |
AT chaneysarahb examininghostandmicrobialdeterminantsofipseudomonasaeruginosaiandistaphylococcusaureusiinduceddelayedwoundhealing |
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1719441020215623680 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu14830431041211392021-08-03T06:39:36Z Examining Host and Microbial Determinants of <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> Induced Delayed Wound Healing Chaney, Sarah B. Veterinary Services Microbiology Pseudomonas aeruginosa Staphylococcus aureus neutorphil chronic wound transposon sequencing porcine pig model cytokine histopathology burn wound Any breakdown of epidermal barrier function leaves the host susceptible to infection. The innate immune system is tasked with the ability to clear these infections and provide an environment that can progress through the remaining stages of wound healing. There is a growing population of both immune competent and immunocompromised individuals that develop non-healing soft tissue injuries. Consistent identification of opportunistic pathogens <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> in chronic wounds has focused our attention on these bacterial species. Specifically, these opportunistic pathogens often exist as sessile, aggregated communities within these wounds and are profoundly resistant to exogenous and host derived antimicrobials. Therefore, we hypothesized that <i>P. aeruginosa</i> and <i>S. aureus</i> are able to subvert the innate immune system leading to persistent inflammation and delayed wound healing. The first part of this thesis investigates the host response to <i>P. aeruginosa</i> and <i>S. aureus</i> in a chronic porcine burn wound model. Previous work in our lab, established this model in collaboration with Drs. Shahwati Roy and Chandan Sen and other members of the Ohio State University’s Comprehensive Wound Center. In the establishment of this wound it was apparent that although epidermal wound healing was achieved after poly-microbial infection, there remained incompetence of the barrier function. Mono-species infections with <i>P. aeruginosa</i> and <i>S. aureus</i> or co-infections with both of these species had previously not been conducted in a chronic wound model using a clinically relevant species. We discovered that bacterial infection results in a host response unique to the infective bacterial species and additive pathologic effects were expressed when present together. Specifically, we were able to identify mono-species infection induced responses by the epidermis that recapitulate defining features of chronic wounds in humans. Ultimately, this work generated a standardized histopathology grading rubric to evaluate changes in the host incited by experimental conditions such as infection or treatments. In the second portion of this thesis, we investigated the hypothesis that human neutrophils could generate a bacterial specific response to <i>P. aeruginosa</i> or <i>S. aureus</i> <i>in vitro</i>. We further speculated that the mode of bacterial growth (i.e. biofilm or planktonic) would influence the neutrophil response. We showed that <i>P. aeruginosa</i> incites a robust pro-inflammatory response. In contrast, <i>S. aureus</i> blunted the neutrophil cytokine response. These bacterial specific responses were largely independent of the mode of bacterial growth. There were minor differences in immune regulatory cytokines and macrophage and lymphocyte chemoattractants between biofilm and planktonic grown <i>P. aeruginosa</i>. Lastly, genetic determinants of fitness in <i>P. aeruginosa</i> were investigated using the chronic porcine wound model, transposon mutant library and deep sequencing technologies. We hypothesized that <i>P. aeruginosa</i> would employ a unique set of genes when establishing chronic infection. We identified transposon mutants in several acute virulence factors that displayed enhanced growth in the wound. Coversely, most genes identified to be important in establishing chronic wound infection were hypothetical, involved in small molecule acquisition or environmental adaptation. This thesis address the importance of bacterial infection in chronic wound development and the role of bacteria in subverting host immune responses. These studies demonstrate that the clinical outcome of delayed wound healing by either <i>P. aeruginosa</i> or <i>S. aureus</i> is dependent on mechanisms unique to either species. Co-infections with both bacterial species produces unique effects on the host (synergism). These studies implicate the need for bacterial specific interventions. 2017-07-03 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1483043104121139 http://rave.ohiolink.edu/etdc/view?acc_num=osu1483043104121139 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |